Current Biology
Volume 20, Issue 13, 13 July 2010, Pages 1154-1164
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Article
Electrical Activity Suppresses Axon Growth through Cav1.2 Channels in Adult Primary Sensory Neurons

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Summary

Background

Primary sensory neurons of the dorsal root ganglia (DRG) regenerate their spinal cord axon if the peripheral nerve axon has previously been cut. This conditioning lesion confers axon growth competence to the neurons. However, the signal that is sensed by the cell upon peripheral lesion to initiate the regenerative response remains elusive.

Results

We show here that loss of electrical activity following peripheral deafferentiation is an important signal to trigger axon regrowth. We first verified that firing in sensory fibers, as recorded from dorsal roots in vivo, declined after peripheral lesioning but was not altered after central lesioning. We found that electrical activity strongly inhibited axon outgrowth in cultured adult sensory neurons. The inhibitory effect depended on the L-type voltage-gated Ca2+ channel current and involved transcriptional changes. After a peripheral lesion, the L-type current was consistently diminished and the L-type pore-forming subunit, Cav1.2, was downregulated. Genetic ablation of Cav1.2 in the nervous system caused an increase in axon outgrowth from dissociated DRG neurons and enhanced peripheral nerve regeneration in vivo.

Conclusions

Our data indicate that cessation of electrical activity after peripheral lesion contributes to the regenerative response observed upon conditioning and might be necessary to promote regeneration after central nervous system injury.

Highlights

► Electrical activity inhibits axon outgrowth in DRG neurons via L-type Ca2+ channels ► Only a peripheral injury silences DRG neurons, allowing axon growth ► Loss of L-type Ca2+ channels enhances axon growth and peripheral regeneration

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These authors contributed equally to this work